Efficacy of CytoSorb®: a systematic review and meta-analysis.

INTRODUCTION: Cytokine adsorption using the CytoSorb® adsorber has been proposed in various clinical settings including sepsis, ARDS, hyperinflammatory syndromes, cardiac surgery or recovery after cardiac arrest. The aim of this analysis is to provide evidence for the efficacy of the CytoSorb® adsorber with regard to mortality in various settings. METHODS: We searched PubMed, Cochrane Library database and the database provided by Cytosorbents™ (01.1.2010-29.5.2022). We considered randomized controlled trials and observational studies with control groups. The longest reported mortality was defined as the primary endpoint. We computed risk ratios and 95%-confidence intervals and used DerSimonian and Lairds random effects model. We analysed all studies combined and divided them into the subgroups: sepsis, cardiopulmonary bypass surgery (CPB), other severe illness, SARS-CoV-2 infection and recovery from cardiac arrest. The meta-analysis was registered in advance (PROSPERO: CRD42022290334). RESULTS: Of an initial 1295 publications, 34 studies were found eligible, including 1297 patients treated with CytoSorb® and 1314 controls. Cytosorb® intervention did not lower mortality (RR [95%-CI]: all studies 1.07 [0.88; 1.31], sepsis 0.98 [0.74; 1.31], CPB surgery 0.91 [0.64; 1.29], severe illness 0.95 [0.59; 1.55], SARS-CoV-2 1.58 [0.50; 4.94]). In patients with cardiac arrest, we found a significant survival advantage of the untreated controls (1.22 [1.02; 1.46]). We did not find significant differences in ICU length of stay, lactate levels, or IL-6 levels after treatment. Of the eligible 34 studies only 12 were randomized controlled trials. All observational studies showed moderate to serious risk of bias. INTERPRETATION: To date, there is no evidence for a positive effect of the CytoSorb® adsorber on mortality across a variety of diagnoses that justifies its widespread use in intensive care medicine.

Perioperative antibiotic prophylaxis in skin surgery - Position paper of the Antibiotic Stewardship working group of the German Society for Dermatologic Surgery (DGDC), Part 2: Special indications and situations.

In addition to prevention of surgical site infections after skin surgery, perioperative antibiotic prophylaxis (PAP) aims to prevent the occurrence of other postoperative infectious complications, especially bacterial endocarditis and hematogenous joint prosthesis infections. This article discusses specific indications for the use of PAP. For example, patients who have undergone any type of heart valve replacement, including transcatheter valve replacement or use of prosthetic material to correct the heart valve, or patients who have experienced bacterial endocarditis, require PAP during skin surgery on mucosal membranes or ulcerated tumors. The use of PAP in special situations such as secondary wound healing, septic dermatosurgery or ulcer surgery is also presented and discussed in detail in this paper based on the current scientific literature. This paper represents the second part of the position paper of the Antibiotic Stewardship Working Group of the German Society for Dermatologic Surgery (DGDC) and summarizes evidence-based recommendations for the administration of PAP during skin surgery for special indications and situations. This is particularly important because, as detailed in Part 1 of this position paper, PAP can and usually should be avoided in skin surgery.

Attitudes of primary care physicians towards antimicrobial stewardship and the impact of a multi-part training course - a pilot study.

Background: A plethora of antimicrobial stewardship (AMS) programs has been initiated during the past years, focusing on hospital settings. Primary-care physicians have seldom been addressed, although the majority of antibiotic prescriptions are issued for outpatients. We sought to investigate attitudes of primary-care physicians and the impact of a customized training course. Methods: Primary-care physicians in southwest Germany were invited to a multi-part training course on AMS in the primary-care setting. Participants were asked to answer a questionnaire about their attitude and factors that hinder them from implementing AMS or enable them to perform AMS. In addition, a knowledge assessment exam at the beginning and end of the training was conducted on selected infectious diseases/syndromes. Results: In total, 36 primary-care physicians participated in the training course. The predominant age group was 51-60 years old (36%; 13/36). The majority, 23/35 (66%), indicated never having had AMS training, while 22/35 (63%) acknowledged partly implementing AMS activities in their daily routine. The primary barrier was lack of expertise, while the main motives were reducing antimicrobial resistance and optimizing patient care. The provision of guidelines was regarded as more important than feedback on their prescription behavior. Exam performance improved from the initial to the final exam on all topics. Conclusion: Customized AMS training courses are a feasible and potentially complimentary tool to address antibiotic misuse in the primary-care setting.

Availability of oral antivirals against SARS-CoV-2 infection and the requirement for an ethical prescribing approach.

The first two oral antivirals, molnupiravir and nirmatrelvir-ritonavir, are now becoming available in many countries. These medicines will be indicated to treat mild-to-moderate COVID-19 in non-hospitalised patients who are at high risk of progressing to severe COVID-19. These antivirals should be prescribed within 5 days of symptom onset, and after SARS-CoV-2 infection has been confirmed. However, the availability of these antivirals will be scarce for some time due to manufacturing constraints. Each country should establish a policy on the conditions under which these antivirals can be prescribed. Such a policy should be based on the fulfilment of five ethical elements: transparency, relevance, appeals, enforcement, and fairness. Following the principles of distributive justice, molnupiravir and nirmatrelvir-ritonavir should be prescribed according to a hierarchy of predicted efficacy, ideally on the basis of an evidence-based scoring system. The placebo-controlled randomised trials that supported the temporary authorisation of these two antivirals were conducted in unvaccinated patients with COVID-19, so an evidence-based prescription practice would only use these drugs for unvaccinated patients until further data become available. However, in the countries that authorised these antivirals in 2021 (the UK and the USA), both vaccinated and unvaccinated patients meeting particular requirements have access to these antivirals. Due to the complexity of prioritisation, national health authorities should start issuing their draft policies as soon as possible and these policies should be regularly updated. The effectiveness of these antivirals against the omicron variant of SARS-CoV-2 must be urgently assessed. Once implemented, molnupiravir and nirmatrelvir-ritonavir must show their effectiveness and safety in the real world, and health systems must be adequately adapted for the correct use of these antivirals.

Diagnosis and treatment of schistosomiasis in children in the era of intensified control.

In the current era of intensified and integrated control against schistosomiasis and other neglected tropical diseases, there is a need to carefully rethink and take into consideration disease-specific issues pertaining to the diagnosis, prevention, control and local elimination. Here, we present a comprehensive overview about schistosomiasis including recent trends in the number of people treated with praziquantel and the latest developments in diagnosis and control. Particular emphasis is placed on children. Identified research needs are offered for consideration; namely, expanding our knowledge about schistosomiasis in preschool-aged children, assessing and quantifying the impact of schistosomiasis on infectious and noncommunicable diseases, developing new antischistosomal drugs and child-friendly formulations, designing and implementing setting-specific control packages and developing highly sensitive, but simple diagnostic tools that are able to detect very light infections in young children and in people living in areas targeted for schistosomiasis elimination.

Neglected tropical diseases: diagnosis, clinical management, treatment and control.

Branded in 2005, "neglected tropical diseases" have gained traction in terms of advocacy, interest for research, enhanced funding and political will for their control and eventual elimination. Starting with an initial set of 13 neglected tropical diseases--seven helminth, three bacterial and three protozoal infections--the list considerably expanded to more than 40 diseases that now also includes viral, fungal and ectoparasitic infections. In this review, we provide a comprehensive overview of the neglected tropical diseases, their causative agents and the current geographical distribution, including their importance for the general practitioners seeing returning travellers and migrants in Switzerland. We characterise the most important of the neglected tropical diseases in terms of at-risk population, estimated number of infections, annual mortality rates and global burden, including current knowledge gaps. With an emphasis on neglected tropical diseases due to helminths, protozoa and ectoparasites, we review common diagnostic methods and current recommendations for treatment at the population level and the individual patient, thereby juxtaposing the situation in highly endemic countries on one side, with Switzerland on the other. We highlight the clinical presentation and management of the neglected tropical diseases in general and then elaborate on two examples, strongyloidiasis and leptospirosis. Our review provides a global perspective of neglected tropical diseases and we hope that it will prove useful for the general practitioner and clinician in Switzerland and elsewhere to enhance their suspicion index, differential diagnosis, clinical management and treatment, including referral to specialised clinics and laboratories when need be.